Metabolic Actions of Xenin

IDENTIFICATION OF XENIN

Xenin is a 25-amino acid peptide that was initially isolated and identified from human gastric mucosa and is present in human plasma []. It has since been identified throughout the digestive system in various mammals (dog, pig, rat, guinea pig, rabbit, and monkey) [–]. Xenin was identified as a mammalian counterpart of the octapeptide xenopsin that was isolated from the skin of the frog

[]. Xenin and xenopsin have identical 6 C-terminal amino acids and share a similar structure with neurotensin []. Xenin is produced by a subpopulation of enteroendocrine cells in the small intestine and neuroendocrine tumors of duodenal origin [, ]. Xenin has been identified in secretory granules, suggesting that xenin is transported to the cell surface and secreted into the circulation []. Amino acid sequences of xenin and its 35-amino acid precursor proxenin are identical to those of N-terminal amino acid residues of coatomer protein complex subunit alpha (COPA) [–]. Xenin levels are low in tissues other than gastric and duodenal mucosa, but digestion with pepsin increases xenin levels in these tissues and treatment of proxenin with pepsin cleaves off 10 C-terminal amino acids and liberates xenin [, ]. These data suggest that bioactive xenin is released from the precursor through the aspartic protease-mediated cleavage. An aspartic protease, cathepsin E is present in gastric mucosa at high concentration and cleaves neurotensin and xenopsin precursors [, ]. Consensus sequence PXXL and VXXL is present at the C-terminus of xenin and proxenin, respectively, and generates the conformation for the cleavage by cathepsin E [, ]. Based on these findings, it has been suggested that cathepsin E plays a major role in releasing xenin through the post-translational cleavage of COPA. Several smaller peptide fragments are released from the 25-amino acid xenin, one of them being xenin-6, the 6 C-terminal amino acid fragment. Xenin-6 is the minimal fragment that demonstrated a biological activity similar to that of xenin [, , ].

Keywords

Gut hormone, satiety, feeding, central nervous system, obesity, diabetes,